This application for continuation of the Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer at the Johns Hopkins University School of Medicine supports a highly interactive, multidisciplinary, and inter institutional program. Five research projects, three cores, a career development and a research developmental program are proposed to carry out our translational research in head and neck cancer. [unreadable] [unreadable] Research Project #1- Tumor Suppressor Gene Promoter Hypermethylation for Detection of Head and Neck Cancer - Co-Investigators, David Sidransky (basic) and Joseph Califano (clinic). Research Project #2 - Molecular Screening and Risk Prediction of HNSC. - Co-Investigators, William Westra (basic) and Wayne Koch (clinic). Research Project #3 - HPV Vaccine Therapy and Correlates of Response in Head and Neck Squamous Cell Carcinomas (HNSC) - Co-Investigators, TC Wu (basic) and Sara Pai (clinic). Research Project #4 - Combined Modality Treatment of Head and Neck Cancer Evaluating Inhibitors of the EGFR/TK Pathway - Co-Investigators, Manuel Hidalgo (basic) and Arlene Forastiere (clinic). Research Project #5 - Exploitation of RET Inhibitors for Treatment of Thyroid Cancer - Co-Investigators, Barry Nelkin (basic) and Doug Ball (clinic). [unreadable] [unreadable] The cores support the research programs (Core #1 - Pathology/ Tissue Core, Dr. Westra; and Core #2 - Administrative/Clinical Core (Drs. Sidransky & Forastiere), Core #3 - Biostatistics and Bioinformatics Core (Dr. Goodman). [unreadable] [unreadable] The Career Development Program (Dr. Forastiere) aids the emergence of new investigators and the Research Developmental Program (Dr. David Sidransky) provides rapid funding of innovative directions. [unreadable] [unreadable] [unreadable] [unreadable]